Catalytic direct 1,4-conjugate addition of aldehydes to vinylketones on secondary-amines immobilised in FSM-16 silica

Article abstract of DOI:10.1039/b202488h

Direct 1,4-conjugate addition of naked aldehydes to vinylketones is catalysed effectively by N-methyl-3-aminopropylated FSM-16 mesoporous silica, which can be regarded as a novel heterogeneous catalysis for a practical C-C bond formation reaction.

Full text of DOI:10.1039/b202488h

Catalytic direct 1,4-conjugate addition of aldehydes to vinylketones on
secondary-amines immobilised in FSM-16 silica
Ken-ichi Shimizu,*a Hiromasa Suzuki,a Eidai Hayashi,b Tatsuya Kodama,b Yoshimi Tsuchiya,c
Hisahiro Hagiwaraa and Yoshie Kitayamab
a Graduate School of Science and Technology, Niigata University, Ikarashi-2, Niigata 950-2181, Japan
b Department of Chemistry & Chemical Engineering, Faculty of Engineering, Niigata University, Ikarashi-2,
Niigata 950-2181, Japan
c
Department of Physics, Faculty of Science, Niigata University, Ikarashi-2, Niigata 950-2181, Japan
Received (in Cambridge, UK) 11th March 2002, Accepted 3rd April 2002
First published as an Advance Article on the web 15th April 2002
Table 1 Physical characteristics of immobilised NMAP catalysts
Direct 1,4-conjugate addition of naked aldehydes to vinylk-
etones is catalysed effectively by N-methyl-3-aminopropy-
lated FSM-16 mesoporous silica, which can be regarded as a
novel heterogeneous catalysis for a practical C–C bond
formation reaction.
b
c
Loadinga/
mmol g21
SBET
/
Vp
/
APDd/
nm
Catalyst
m2 g21
cm3 g21
1
2
3
4
0.74
0.48
0.18
0
0.75
0.52
0.76
572
720
788
881
777
783
164
0.89
0.96
1.01
1.23
1.05
1.01
—
2.74
2.77
2.54
2.81
2.67
2.54
—
Substituted 5-ketoaldehydes 3 have been important synthons
especially for substituted cyclohex-2-en-1-one derivatives
which have been versatile starting materials for synthesis of
natural products such as terpenoids. Because of the difficulty in
controlling high reactivity of formyl groups, the synthesis of
5-ketoaldehydes 3 has been accomplished via several-pot
reaction via 1,4-addition of masked aldehydes such as enamines
or silylenol ethers in the presence of Lewis acid.1 However, it
was recently found by Hagiwara et al. that diethylamine
catalyses the direct 1,4-conjugate addition of naked aldehydes
to vinylketones, though a large amount of catalyst was used.2 In
order to improve the catalytic performance of this novel
reaction, we have attempted heterogenization of the catalyst to
provide a recyclable and efficient solid catalyst.
From environmental and economical points of view, the use
of heterogeneous catalysts offers several advantages in organic
synthesis, e.g. simplification of reaction procedures, easy
separation of products, repeated use, and so on.3–12 Mesoporous
silicas such as FSM-1613 and MCM-41,14 having high surface
areas of > 1000 m2 g21 and large pore sizes, can be unique
inorganic supports for introducing reactive species for the
catalysis involving bulky substances.5–12 For example, novel
heterogeneous basic catalysts, in which amines are covalently
anchored to mesoporous silicas, were reported as noble
catalysts.5–10 However, in most of the studies, this new class of
solid catalysts was employed for ‘ordinary’ reactions such as
Knoevenagel,6,8,9 aldol9 and nitroaldol10 condensations, which
can also be catalysed by classical oxidic solid bases4 such as
alkali ion-exchanged zeolites, alkaline earth oxides and hydro-
talcite. Here, we report that direct 1,4-conjugate addition of
naked aldehydes 1 to vinylketones 2, which cannot be catalysed
by ordinary oxidic solid bases, is catalysed efficiently by N-
methyl-3-aminopropylated FSM-16 mesoporous silica
(NMAP-FSM). The truly catalytic behaviour of this material as
well as the recycling characteristics are presented to exemplify
the effectiveness of this catalytic system.
5 (AP)e
6 (DMAP)f
7 (SiO2)g
a Estimated from nitrogen content. b BET surface area obtained from the N2
adsorption isotherm. Before the experiment, the sample was dried at 150 °C
for 1 h. c Pore volume obtained from the BJH equation. d Average pore
diameter obtained from the BJH equation. e Aminopropylated FSM-16.
f N,N-Dimethylaminopropylated FSM-16. g NMAP immobilised on amor-
phous silica.
catalysts were as expected for mesoporous materials (Table 1).
These values were reduced after amino group introduction,
which should be due to the presence of amino groups in the
Scheme 1
Table 2 Conjugate addition of decanal to MVKa
Entry
Catalyst ([N]/mol%)b
t/h
3 Yield (%)
TONc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1 (0.8)
2 (0.5)
3
24
24
24
6
24
6
1
1
1
1
20
20
24
24
57
33
41
0
24
2
44
70
72
64
63
29
21
0
75
72
81
3 (0.5)
4 (0)d
—
4.9
0.5
50
7.0
7.2
6.4
6.3
14
5 (5.0)
6 (5.0)
7 (1.0)
1 (10)
1st reuse (10)e
2nd reuse (10)e
3rd reuse (10)e
Et2NH (2.0)f
PrNHMe (2.0)g
MgOdhi
Pure silica FSM-16 was prepared from kanemite by using
C16H33NMe3Cl according to a method previously described.13
Amorphous silica (Cab-O-Sil, 200 m2 g21) was also used for a
comparison. Surface functionalization with amino groups was
carried out according to the method described in the lit-
erature.7,15 The catalysts were prepared with a fairly high atom-
efficiency: elemental analysis on solid materials (Table 1)
revealed that more than 80% of amino-silanes introduced were
anchored on the supports. Since XRD patterns of NMAP-FSM
were essentially the same as that of FSM-16, the long-range
ordered structure of the support was confirmed to be preserved.
13C-MAS NMR spectra of NMAP-FSM showed the presence of
N-methyl-3-aminopropyl groups (53.0, 34.0, 20.5 and 10.5
ppm). The surface area, pore volume, and pore diameters of the
11
—
—
Hydrotalcitedhj
0
a Reactions were conducted with decanal (1 mmol), MVK (1.5 mmol) in
toluene (5 mL) at reflux temperature under N2. b Amount of the catalyst
tested. c Amount of product per mole of amino groups. d The catalyst
loading was 0.1 g. e Reuse of NMAP-FSM. f Diethylamine. g N-Methyl-
3-propylamine. h Prior to the reaction, catalysts were evacuated at 500 °C
for 1 h. i MgO (JRC-MGO-1) was supplied from the Catalysis Society of
Japan. j Mg–Al hydrotalcite (Mg6Al2(OH)16CO3·4H2O) was supplied from
Kyowa Chemcl Industry Co., Ltd.
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CHEM. COMMUN., 2002, 1068–0169
This journal is © The Royal Society of Chemistry 2002

Table 3 Conjugate addition of aldehydes to vinylketones with the catalyst
channels of FSM-16. These results indicate that amino groups
were anchored to the channels of FSM-16 silica.
1a
Table 2 shows the results of the 1,4-conjugate addition of
decanal (1, R1NC8H17) to methylvinylketone (MVK) (2,
R2NCH3).16 The 1,4-adduct, 5-ketoaldehyde 3, is selectively
produced on NMAP-FSM catalysts (entries 1, 2, 3 and 8),
although the reactions do not occur with conventional solid
bases such as MgO and hydrotalcite (entries 14 and 15). No
measurable by-products were observed by GC and HPLC
analyses. The present reaction system required no additional
regent other than solvent and produced no side-products
(Scheme 1).
The amine-free FSM-16 silica is completely inert (entry 4),
and hence, anchored amino groups are the catalytic species of
NMAP-FSM. The activity depends strongly on the type of
amines supported. The order of the activity is second-
ary > primary > tertiary (entries 1, 5 and 6), suggesting the
intervention of the enamine pathway.2 For secondary-amine
supported catalysts, the equivalence of the amine sites was
probed by changing the loading of the active site (NMAP group)
per unit catalyst mass (entries 1, 2 and 3). The TON values of
NMAP-FSM are almost independent of the NMAP loading,
which suggests that each immobilised secondary-amine can act
as the active site with similar reactivity. The catalysts based on
hexagonal mesoporous silica show higher activity than that on
amorphous silica, TON being 1.5 times higher by comparing
catalysts with similar loading (entries 1 and 7). It is noteworthy
that the TON value of the NMAP-FSM is much higher than
those of the homogenous amine catalysts, N-methyl-3-propyla-
mine or diethylamine (entries 12 and 13). We believe, at
present, that the higher TON of NMAP-FSM catalyst than its
homogenous counterpart as well as NMAP supported on
amorphous silica is due to the increase in the reactant
concentration inside the channels of FSM-16 mesoporous
silica.
Entry
Aldehydes
Vinylketones
3 Yield (%)
TON
1
2
3
4
5
6
n-Octanal
n-Hexanal
n-Butanal
Ph(CH2)2CHOb
n-Hexanal
n-Hexanalc
MVK
MVK
MVK
MVK
EVK
EVK
59
87
88
37
93
40
59
87
88
37
93
400
a Reaction were conducted with aldehydes (1 mmol), vinylketones (1.5
mmol) in toluene (5 mL) at reflux temperature under N2 with 1 mol% of the
catalyst. b Acetonitrile was used as solvent. c Amount of the catalyst tested
was 0.1 mol%.
without loss of activity, (3) one-pot reaction without additives,
side-products, and by-products.
Notes and references
1 G. Stork, A. Brizzolara, H. Landesman, J. Szmuskovics and R. Terrell,
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2 H. Hagiwara, T. Okabe, K. Hakoda, T. Hoshi, H. Ono, V. P. Kamat, T.
Suzuki and M. Ando, Tetrahedron Lett., 2001, 42, 2705; H. Hagiwara,
N. Komatsubara, H. Ono, T. Okabe, T. Hoshi, T. Suzuki, M. Ando and
M. Kato, J. Chem. Soc., Perkin Trans. 1, 2001, 316.
3 Fine Chemicals through Heterogeneous Catalysis, ed. R. A. Sheldon
and H. van Bekkum, Wiley-VCH, Weinheim, 2001.
4 H. Hattori, Chem. Rev., 1995, 95, 537; Y. Ono and T. Baba, Catalysis,
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Vos and P. A. Jacobs, Catal. Rev., 2001, 43, 443.
5 P. M. Price, J. H. Clark and D. J. Macquarrie, J. Chem. Soc., Dalton
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Elemental analysis showed that nitrogen content of the
NMAP-FSM catalyst did not decrease after the reaction,17
confirming that leaching of amino groups during the reaction
was negligible. The reaction did not proceed further when the
solid catalyst was removed before completion of the reaction,
proving heterogeneous catalytic activity of NMAP-FSM and no
contribution from homogenous catalysis. The catalyst can be
easily separated from the reaction mixture by simple filtration
and is recycled. Although the simply filtered catalyst showed a
decrease in activity (yield = 43%), the activity of the recovered
catalyst (entries 9, 10 and 11) was comparable to that observed
for the first run (entry 8) when the filtered catalyst was simply
dispersed in a dilute aqueous solution of K2CO3 (2 mM) for 5
min, followed by washing with distilled water and subsequent
drying at 373 K.18 By this treatment, the catalyst was reusable
for all the three cycles in the repeated runs without a marked
loss of activity.
The general applicability of the present 5-ketoaldehyde
synthesis has been demonstrated by expanding the reaction to
different aldehydes and vinylketones (Table 3). In all cases, the
5-ketoaldehyde 3 is obtained as a sole product in high yields.
The best yield (93%) is obtained in the reaction of n-hexanal
with ethylvinylketone (EVK) on NMAP-FSM catalyst (entry
5). It is worthy of note that the reaction proceeds even with a
small amount of the catalyst (0.1 mol%), and a TON of 400 was
obtained (entry 6), which indicates a high stability of the
immobilised catalyst.
6 D. J. Macquarrie, J. H. Clark, A. Lambert, J. E. G. Mdoe and A. Priest,
React. Funct. Polym., 1997, 35, 153; D. J. Macquarrie and D. Jackson,
Chem. Commun., 1997, 1781; D. J. Macquarrie, Green Chem., 1999, 1,
195.
7 A. Cauvel, G. Renard and D. Brunel, J. Org. Chem., 1997, 62, 749; D.
Burunel, Microporous Mesoporous Mater., 1999, 27, 329.
8 Y. V. S. Rao, D. E. D. Vos and P. A. Jacobs, Angew. Chem., Int. Ed.
Engl., 1997, 36, 2661.
9 I. Rodriguez, S. Iborra, A. Corma, F. Rey and J. L. Jorda, Chem.
Commun., 1999, 593.
10 G. Demicheli, R. Maggi, A. Mazzacani, P. Righi, G. Sartori and F. Bigi,
Tetrahedron Lett., 2001, 42, 2401.
11 S. P. Gupte, A. B. Shivarkar and R. V. Chaudhari, Chem. Commun.,
2001, 2620.
12 T. M. Jyothi, M. L. Kaliya, M. Herskowitz and M. V. Landau, Chem.
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13 S. Inagaki, Y. Fukushima and K. Kuroda, J. Chem. Soc., Chem.
Commun., 1993, 680.
14 C. T. Kresge, M. E. Leonowicz, W. J. Roth, J. C. Vartuli and J. S. Beck,
Nature, 1992, 359, 710.
15 Typically, 2.0 g of the FSM-16 sample was evacuated at 150 °C and then
toluene (20 mL) containing N-methyl-3-aminopropyl(triethoxy)silane
was introduced. The mixture was heated at reflux for 3 h and the solid
was filtered off, washed with toluene and acetone and dried at 100 °C
overnight.
16 Before the reaction, the catalyst was dried in air at 150 °C for 1 h. The
reaction was carried out by stirring the reaction mixture containing
aldehydes (1 mmol) and vinylketones (1.5 mmol) in dry toluene (5 mL)
at reflux temperature under nitrogen atmosphere. Progress of the
reactions was monitored by GC analyses of aliquots using o-xylene as
internal standard.
17 Nitrogen contents per gram of the support before and after the reaction
were 0.80 mmol g21 and 0.83 mmol g21, respectively.
18 This observation may be explained as follows. The organic acids,
present as impurities in aldehydes or produced during the reaction,
neutralised the amine catalysts. The organic acids were removed by
treatment with dilute aqueous K2CO3 solution.
In conclusion, we have developed a highly convenient
1,4-addition of naked aldehydes to vinylketones catalysed by
the secondary-amine immobilised FSM-16 mesoporous silica.
The present system can be regarded as a novel heterogeneous
catalysis for a practical and environmentally friendly C–C
formation reaction in view of the following advantages: (1) easy
separation of the catalyst by simple filtration, (2) reusability
CHEM. COMMUN., 2002, 1068–0169
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